Integrating Bioinformatic Strategies with Real-World Data to Infer Distinctive Immunocyte Infiltration Landscape and Immunologically Relevant Transcriptome Fingerprints in Ossification of Ligamentum Flavum

Abstract

Purpose Ossification of the ligamentum flavum (OLF) is a multifactorial disease characterized by an insidious and debilitating process of abnormal bone formation in ligamentum tissues. However, its definite pathogenesis has not been fully elucidated. Potential links between the immune system and various forms of heterotopic ossification have been discussed for many years, whereas no research investigated the immune effects on the initiation and development of OLF. Therefore, we attempt to shed light on this issue. Methods A series of bioinformatic algorithms were integrated to evaluate the immune score and the immunocyte infiltration patterns between OLF and normal samples, screen OLF-related and immune-related differentially expressed genes (OIDEGs), and analyze their biological functions. Correlation analysis inferred OIDEGs-related differentially expressed lncRNAs (OIDELs) and infiltrating immune cells (OIICs) to construct an immunoregulatory network. Results Differential immune score and immune cell infiltration were determined between two groups, and 10 OIDEGs with diverse biological function annotations were identified and verified. A lncRNA-gene-immunocyte regulatory network further revealed 10 OIDEGs, 41 OIDELs and 7 OIICs that were highly correlated. Among them, CD1E and STAT3 were predicted as hub genes whether at the expression level or interaction level. cDCs emerged as having the most prominent differences and the highest degree of connectivity. FO393414.3, AC096734.1, LINC01137 and DLX6-AS1 with the greatest number of OIDEGs were thought to be more likely to participate in immunoregulation of OLF. Conclusion This is the first research to preliminarily elucidate OLF-related immunocyte infiltration landscape and immune-associated transcriptome signatures based on bioinformatic strategies and real-world data, which may provide compelling insights into the pathogenesis and therapeutic targets of OLF.

Exploring lncRNA Expression Patterns in Patients With Hypertrophied Ligamentum Flavum

“…The role of lncRNAs has been identified in diverse biological processes, including cell proliferation, apoptosis, and tumorigenesis [ 9 , 10 ]. LncRNAs have also been associated with musculoskeletal diseases, such as osteoarthritis [ 11 ], intervertebral disc degeneration [ 12 ], and Ossification of the ligamentum flavum [ 13 ]. lncRNAs are also involved in the pathological process of fibrosis of the lung [ 14 , 15 ], liver [ 16 , 17 ], kidney [ 18 , 19 ], and heart [ 20 , 21 ].…”

Deciphering Obesity-Related Gene Clusters Unearths SOCS3 Immune Infiltrates and 5mC/m6A Modifiers in Ossification of Ligamentum Flavum Pathogenesis

“…Our previous research has identified 10 OLF-related and immune-related differentially expressed genes (OIDEGs) ( 20 ). Eleven ORDEGs, OIDEGs, TNF signaling-enriched DEGs (TSDEGs), and immune response-enriched DEGs (IMDEGs) were overlapped to obtain SOCS3 as the core gene ( Figure 7D ).…”

Revealing the novel metabolism‐related genes in the ossification of the ligamentum flavum based on whole transcriptomic data

“…Previous studies have indicated that the population with obesity or diabetes were more likely to suffer from the OLF, which indicated that metabolic disorder might play important roles in the pathogenesis of OLF. 3 , 10 , 14 , 18 Some bioinformatic analyses were conducted to investigate the role of ceRNA network or immunity abnormality in the onset and development of OLF, 31 , 42 however, no study was especially conducted to determine the role of metabolic disorder in the pathogenesis of OLF with strict bioinformatic algorithms. In the current study, we firstly observed the difference of metabolism score between OLF tissues and normal LF tissues, which presented that metabolic disorder might be an important etiological factor for OLF.…”

“… 30 Zhang et al analyzed the immunocyte infiltration landscape, and constructed an immunoregulatory network between the immunocytes and immune‐related genes in OLF. 31 However, the relationship between metabolic disorder and immunity abnormality in OLF has not been investigated to date.…”

“…A previous bioinformatic analysis was conducted to investigate the role of immunity abnormality in the development of OLF using the sequencing data. 31 However, metabolic disorder, as another important contributor to OLF, has not be investigated using bioinformatic approaches up to now.…”